# Design and Synthesis of Marine Sarocladione Derivatives with Potential Anticancer Activity

## TL;DR

Researchers synthesized new versions of a marine compound called sarocladione, finding one that strongly stops cancer cell growth by blocking the cell cycle.

## Contribution

A new, potent derivative of sarocladione was synthesized and shown to induce cell cycle arrest and apoptosis in cancer cells.

## Key findings

- Compound 8 showed four-fold higher potency against HCT116 cells compared to the natural product.
- The (5R)-configuration at C-5 is critical for the compound's activity.
- Compound 8 induces G2/M phase cell cycle arrest followed by apoptosis in cancer cells.

## Abstract

The discovery of structurally novel anti-tumor agents remains a crucial objective in cancer drug research. In this study, we systematically explored the bioactivity potential of sarocladione (5), a structurally unique marine-derived 14-membered ring diketone steroid. Guided by a function-oriented strategy, seven new derivatives (6–13) were synthesized based on an efficient biomimetic synthesis of sarocladione. Evaluation of their antiproliferative activities against human cancer cell lines demonstrated that the intact macrocyclic scaffold is indispensable for activity. Extension of the conjugated π-system led to the identification of compound 8, which exhibited approximately four-fold enhanced potency against HCT116 cells (IC50 = 1.86 µM) compared with the parent natural product. Stereochemical analysis further revealed the critical role of the (5R)-configuration at C-5. Phenotypic investigations indicated that compound 8 induces concentration-dependent G2/M phase cell cycle arrest, followed by apoptosis, suggesting a cell cycle-dependent antiproliferative effect. Overall, this study highlights sarocladione as a promising marine-derived scaffold for further antiproliferative optimization.